Tumor lysis syndrome in chronic lymphocytic leukemia: conventional treatment versus novel agents A protocol for systematic review and meta-analysis

Introduction: Existing evidence on the difference in the incidence of tumor lysis syndrome (TLS) in Chronic Lymphocytic Leukemia (CLL) patients receiving novel therapies versus patients receiving conventional therapies is limited and inconclusive. The aims of this planned systematic review and meta-analysis are therefore (1) assess the TLS incidence reported in clinical trials for the novel or targeted agents comparing to conventional chemotherapeutic agents used to treat patients with CLL (2) to identify the TLS prophylaxis strategies that are utilized in clinical trials of the novel or targeted agents for CLL if it was fully reported or under-reported and (3) to compare the mortality among patients with TLS in conventional versus novel agents. Methods: We will conduct a systematic review and meta-analysis. Several electronic databases will be searched using predefined search terms to identify relevant studies. Eligible studies should report findings on the incidence of TLS in CLL patients. Primary observational studies with cross-sectional or prospective research design, case-control studies, and studies with experimental designs will be included. Study quality will be evaluated by 2 reviewers using the statistical methodology and categories described in the Cochrane Collaboration Handbook and preferred reporting items for systematic reviews and meta-analyses and other applicable guidelines. The meta-analysis will be performed and conducted using applicable standard statistical software like comprehensive meta-analysis and STATA. Discussion: This review and meta-analysis will be among the first to systematically explore and integrate the evidence available on the comparison between the incidences of TLS in CLL patients treated with novel agents versus conventional agents. By gathering and summarizing information about the risk of TLS in this patient population, the findings from this review will provide insights for future research directions and more understanding of the difference of TLS incidence between novel treatments and conventional treatment and suggest prophylactic measures for such cases. Systematic review registration: The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42020166770). The protocol was registered with the Hamad medical corporation, Medical research Center registry under a unique reference number (MRC-01-20-709).